Certain aspects of glucose, fatty acid and amino acid metabolism will be studied in skeletal muscle using a recently developed isolated perfused rat hindquarters preparation. The aim of these investigations is threefold: 1. To reinvestigate the regulation of glucose utilization and disposition in muscle, with special emphasis on the problem of insulin resistance. This would involve an evaluation of the role of free fatty acids and ketone bodies as insulin antagonists as well as studies of glucose, fatty acid and amino acid metabolism in animals with diabetes and/or spontaneous insulin resistance, e.g., obesity. These studies will be carried out on both resting and exercising muscle. 2. To study the contribution of muscle to the disordered amino acid metabolism of obesity, diabetes and a variety of other nutritional and hormonal states. 3. To assess the mechanisms by which alanine and glutamine can be formed within muscle. These studies will attempt to delve into the origin of the nitrogen used in the synthesis of these amino acids. In particular, we will investigate the role of other amino acids as nitrogen sources. In addition to these investigations with the hindquarter preparation, we will evaluate the effect of physical training on a treadmill on glucose tolerance, insulin sensitivity and plasma triglycerides in intact rats. The aim of this study is to explore in animal models the possibility that physical training may provide a useful form of therapy in certain patients with diabetes and/or hypertriglyceridemia.